Three‐dimensional ex vivo imaging and analysis of intraportal islet transplants

In clinical islet transplantation, because the long‐term insulin‐independence rate is still poor, a method for detailed analysis of the transplanted islets in the liver after transplantation is required. We have established a novel imaging technique suitable for analysis of transplanted islets in liver using an optical projection tomography (OPT) method. A three‐dimensional tomographic image of the transplanted islets in liver was reconstructed. The number of islets transplanted and the number of transplanted islets observed using OPT showed good correlation. The OPT method was used to compare the numbers of transplanted islets in mouse syngeneic and allogeneic transplantation models. Blood glucose concentrations of streptozotocin (STZ)‐induced diabetic mice transplanted with syngeneic islets remained normoglycemic and the number of transplanted islets was largely preserved 11 days after transplantation. In mice transplanted with allogeneic islets, hyperglycemia recurred from 7 days after transplantation and the number and the volume of transplanted islets was significantly reduced 11 days after transplantation. These results indicate that OPT imaging and analysis may be a useful tool to quantitatively and sterically evaluation of transplanted islets in liver at the cellular level.     

Reduced prefrontal hemodynamic response in children with ADHD during the Go/NoGo task: a NIRS study

The current study examined the hemodynamic response during the Go/NoGo task in children with/without attention deficit/hyperactivity disorder (ADHD). Using near-infrared spectroscopy, oxy-Hb and deoxy-Hb concentration changes in the frontal areas were compared during the conditions with/without inhibitory demand. Compared with typically developing children, children with ADHD showed significantly reduced activation during the conditions with inhibitory demand (NoGo-condition) in the frontal areas. However, no significant differences in activation during the conditions without inhibitory demand (Go-condition) were found between the two groups. The current findings revealed that children with ADHD exhibit an altered hemodynamic response specifically during response inhibition, but not during response execution, and suggested the clinical usefulness of near-infrared spectroscopy for the evaluation of response inhibition deficits in children with ADHD.     

Effectiveness of social skills training for children with developmental disorders: behavioral analysis using a two-dimensional motion capture system

The current study sought to develop a new behavioral analysis methods to evaluate the effects of social skills training (SST). SST is known to be an effective method to improve the social skills of children with behavioral problems. However, current evaluation methods involve behavioral rating scales that are heavily dependent on evaluators' particular experiences they have had. To quantitatively examine the behavioral effects of SST, we examined subjects' head-movements related to social behavior, using a two-dimensional motion capture system (Kissei Comtec, Japan). Four children (three male, one female, 7-8 years of age) with pervasive developmental disorder (PDD) or attention deficit/hyperactivity disorder (AD/HD) participated in 16 sessions of SST. Before and after SST, head-coordinates on a two-dimensional plane were calculated using their behavior during a pair task, measured by four digital cameras. After SST, the number of communication behaviors was increased compared to before SST. In addition, children looked longer at another child within 30 degrees of the central visual field. Time-series analysis of the visual field during the detection of another child revealed significant auto-correlation from about -1.12 second. before to the beginning of communication behavior (p<0.05). The results suggested that our method can provide a quantitative index of characteristics related to skilled social behaviors. We conclude that a two-dimensional motion capture system would be useful for visualization of the interventional effects of SST, which would supplement assessments by the conventional observational strategies.     

Enhancing effects of trichloroethylene and tetrachloroethylene on type I allergic responses in mice

Trichloroethylene (TCE) and tetrachloroethylene (perchloroethylene; PCE) are commonly identified as environmental contaminants of groundwater. Previously, we investigated the enhancing effects of TCE and PCE on antigen-induced histamine release and inflammatory mediator production in rat mast cells. In this study, to examine the potential effect of TCE and PCE on antigen-induced histamine release from mouse mast cells, mouse bone marrow-derived mast cells (BMMC) were sensitized with anti-dinitrophenol (DNP) monoclonal IgE antibody and then stimulated with DNP-BSA containing with TCE or PCE. Both TCE and PCE significantly enhanced antigen-induced histamine release from BMMC. Next we investigated the effects of TCE and PCE on the passive cutaneous anaphylaxis (PCA) reaction in vivo using ICR mice. TCE and PCE significantly enhanced the PCA reaction in a dose-dependent manner. In addition, we examined the enhancing effects of ingesting small amount of TCE and PCE in drinking water on antigen-stimulated allergic responses. After the ICR mice had ingested TCE or PCE in their drinking water for 2 or 4 weeks, we performed the PCA reaction. Both TCE and PCE ingestion enhanced the PCA reaction in a dose-dependent manner for 4 weeks. These results suggest that exposure to TCE and PCE leads to the augmentation of type I allergic responses in many species.     

Bismuth protects against arsenite-induced inhibition of proteoglycan synthesis in cultured vascular endothelial cells

Chronic ingestion of arsenic is associated with an increased risk of vascular disease such as atherosclerosis. Previously, we showed that arsenite inhibits the synthesis of general proteoglycans (PGs), which are key molecules in the progression of atherosclerosis, in vascular endothelial cells. In the present study, we investigated the effect of several metals on arsenite-induced inhibitory effect in endothelial cells. The results indicate that, after 24-hr incubation, the inhibition of PG synthesis caused by sodium arsenite was protected by bismuth nitrate but not zinc sulfate, manganese chloride, nickel chloride or cobalt chloride. The accumulation of arsenic in the cell layer was significantly decreased by bismuth after 12-hr incubation and that of bismuth was also decreased by arsenite. It was therefore suggested that the protective effect of bismuth against the inhibitory effect of arsenite on PG synthesis in vascular endothelial cells may be due, at least in part, to the decrease in cellular arsenic accumulation.     

Molecular basis of maternal age-related increase in oocyte aneuploidy

Aneuploidy is one of the most common and serious pregnancy complications in humans. Most conceptuses with autosomal aneuploidy die in utero, resulting in early pregnancy loss. However, some fetuses with aneuploidy survive to term but suffer from disorders associated with congenital anomalies and mental retardation, such as Down syndrome with trisomy 21. Three general characteristics of this condition are well acknowledged: (i) in most cases the extra chromosome is of maternal origin; (ii) most cases are derived from a malsegregation event in meiosis I; and (iii) the frequency of these errors increases with maternal age. The basis for the age-dependent increase in meiosis I errors has been a long-standing enigma. Many investigators have addressed the nature of this biological phenomenon through genomic analyses of extra chromosome 21 using polymorphic markers to determine the frequency or location of crossovers that should ensure faithful chromosome segregation. Cytogenetic analyses of in vitro unfertilized oocytes have also been performed. However, no definitive conclusions regarding meiosis I errors have yet been reached from such studies. Recent findings in conditional knock-out mice for meiosis-specific cohesin have shed further light on this issue. The present review focuses on the current understanding of age-related aneuploidy and provides an overview of the mechanisms involved. We refer to recent data to illustrate some of the new paradigms that have arisen in this field.